With or without sugar? (A)glycosylation of therapeutic antibodies

Molecular Biotechnology

Volumn 54, Issue 3, 2013, Pages 1056-1068

  Hristodorov, Dmitrij ^b   Fischer, Rainer ^b   Linden, Lars ^a  

^a Global Biologics Bayer Healthcare   (Germany)

^b FRAUNHOFER INSTITUTE FOR MOLECULAR BIOLOGY AND APPLIED ECOLOGY IME   (Germany)

Author keywords

Aglycosylated antibodies; Antibody therapeutics; Fc glycosylation; Glyco engineering

Indexed keywords

ANTIBODY THERAPEUTICS; CARDIO-VASCULAR DISEASE; GLYCO-ENGINEERING; PHARMACOKINETIC PROFILES; PHARMACOKINETIC PROPERTIES; RECOMBINANT ANTIBODY; THERAPEUTIC ANTIBODIES; THERAPEUTIC MONOCLONAL ANTIBODIES;

AMINO ACIDS; DISEASES; GLYCOSYLATION; MONOCLONAL ANTIBODIES; PHARMACOKINETICS; PRODUCTION PLATFORMS; PROTEINS;

ESTERIFICATION;

ANTIBODY; BENRALIZUMAB; BIW 8962; CLAZAKIZUMAB; FC RECEPTOR; GLYCAN; IMGATUZUMAB; IMMUNOGLOBULIN G ANTIBODY; KHK 2866; KHK 2898; KW 2871; LFB R 593; LFB R 603; MEDI 551; MOGAMULIZUMAB; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY GT MAB2.5GEX; MONOCLONAL ANTIBODY GT MAB5.2GEX; MONOCLONAL ANTIBODY GT MAB7.3GEX; OA 5D 5; OBINUTUZUMAB; OTELIXIZUMAB; RECOMBINANT ANTIBODY; TRX 1; TRX 518; UNCLASSIFIED DRUG;

AGING; AGLYCOSYLATION; ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; ANTIBODY STRUCTURE; BIOSYNTHESIS; CANCER IMMUNOTHERAPY; CLINICAL EVALUATION; CLINICAL TRIAL (TOPIC); COMPLEMENT DEPENDENT CYTOTOXICITY; DEAMINATION; DIFFERENTIAL SCANNING CALORIMETRY; ENDOPLASMIC RETICULUM; ESCHERICHIA COLI; FUCOSYLATION; GENE EXPRESSION; GLYCOSYLATION; GRANULOCYTE; HUMAN; IMMUNE RESPONSE; IMMUNOGENICITY; INSULIN DEPENDENT DIABETES MELLITUS; IONIC STRENGTH; ISOMERIZATION; MAMMAL CELL; NATURAL KILLER CELL; NONHUMAN; OXIDATION; PHAGOCYTOSIS; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PICHIA ANGUSTA; PICHIA PASTORIS; PLASMA HALF LIFE; POLYMERIZATION; PROTEIN SYNTHESIS; REVIEW; RNA INTERFERENCE; SACCHAROMYCES CEREVISIAE; SIALYLATION; SULFATION;

ANIMALS; ANTIBODIES, MONOCLONAL; GLYCOSYLATION; HUMANS; IMMUNOGLOBULIN FC FRAGMENTS; POLYSACCHARIDES;

EUKARYOTA; MAMMALIA;

EID: 84882867804     PISSN: 10736085     EISSN: 15590305     Source Type: Journal    
DOI: 10.1007/s12033-012-9612-x     Document Type: Review

References (150)

1. Carter, P. J. (2006). Potent antibody therapeutics by design. Nature Reviews Immunology, 6, 343-357.
2. Moutel, S.; Perez, F. (2008). Antibodies-Europe. Engineering the next generation of antibodies. Biotechnology Journal, 3, 298-300.
3. Reichert, J. M.; Valge-Archer, V. E. (2007). Development trends for monoclonal antibody cancer therapeutics. Nature Reviews Drug Discovery, 6, 349-356.
4. Reichert, J. M. (2010). Antibodies to watch in 2010. MAbs, 2, 84-100.
5. Weiner, L. M.; Surana, R.; Wang, S. (2010). Monoclonal antibodies: Versatile platforms for cancer immunotherapy. Nature Reviews Immunology, 10, 317-327.
6. Jefferis, R. (2005). Glycosylation of recombinant antibody therapeutics. Biotechnology Progress, 21, 11-16.
7. Jefferis, R. (1991). Structure-function relationships in human immunoglobulins. Netherlands Journal of Medicine, 39, 188-198.
8. Edelman, G. M.; et al. (1969). The covalent structure of an entire gammaG immunoglobulin molecule. Proceedings of the National Academy of Sciences of the United States of America, 63, 78-85.
9. Raju, T. S.; et al. (2000). Species-specific variation in glycosylation of IgG: Evidence for the species-specific sialylation and branch-specific galactosylation and importance for engineering recombinant glycoprotein therapeutics. Glycobiology, 10, 477-486.
10. Hamako, J.; et al. (1993). Comparative studies of asparagine-linked sugar chains of immunoglobulin G from eleven mammalian species. Comparative Biochemistry and Physiology B, 106, 949-954.
11. Kaneko, Y.; Nimmerjahn, F.; Ravetch, J. V. (2006). Anti-inflammatory activity of immunoglobulin G resulting from Fc sialylation. Science, 313, 670-673.
12. Feige, M. J.; Walter, S.; Buchner, J. (2004). Folding mechanism of the CH2 antibody domain. Journal of Molecular Biology, 344, 107-118.
13. Ghirlando, R.; et al. (1999). Glycosylation of human IgG-Fc: Influences on structure revealed by differential scanning micro-calorimetry. Immunology Letters, 68, 47-52.
14. Hari, S. B.; et al. (2010). Acid-induced aggregation of human monoclonal IgG1 and IgG2: Molecular mechanism and the effect of solution composition. Biochemistry, 49, 9328-9338.
15. Kayser, V.; et al. (2011). Glycosylation influences on the aggregation propensity of therapeutic monoclonal antibodies. Biotechnology Journal, 6, 38-44.
16. Correia, I. R. (2010). Stability of IgG isotypes in serum. MAbs, 2, 221-232.
17. Millward, T. A.; et al. (2008). Effect of constant and variable domain glycosylation on pharmacokinetics of therapeutic antibodies in mice. Biologicals, 36, 41-47.
18. Jefferis, R. (2009). Glycosylation as a strategy to improve antibody-based therapeutics. Nature Reviews Drug Discovery, 8, 226-234.
19. Liu, H.; Bulseco, G. G.; Sun, J. (2006). Effect of posttranslational modifications on the thermal stability of a recombinant monoclonal antibody. Immunology Letters, 106, 144-153.
20. Stanley, P.; Schachter, H.; Taniguchi, N. (2009). N-glycans. In A. Varki et al. (Eds.), Essentials of glycobiology. New York: Cold Spring Harbor.
21. Schachter, H. (1986). Biosynthetic controls that determine the branching and microheterogeneity of protein-bound oligosaccharides. Biochemistry and Cell Biology, 64, 163-181.
22. Schachter, H. (1986). Biosynthetic controls that determine the branching and microheterogeneity of protein-bound oligosaccharides. Advances in Experimental Medicine and Biology, 205, 53-85.
23. Kornfeld, R.; Kornfeld, S. (1985). Assembly of asparagine-linked oligosaccharides. Annual Review of Biochemistry, 54, 631-664.
24. Schachter, H. (2000). The joys of HexNAc. The synthesis and function of N- and O-glycan branches. Glycoconjugate Journal, 17, 465-483.
25. Stanley, P.; Raju, T. S.; Bhaumik, M. (1996). CHO cells provide access to novel N-glycans and developmentally regulated glycosyltransferases. Glycobiology, 6, 695-699.
26. Zhou, Q.; et al. (2004). N-Linked oligosaccharide analysis of glycoprotein bands from isoelectric focusing gels. Analytical Biochemistry, 335, 10-16.
27. Lux, A.; Nimmerjahn, F. (2011). Impact of differential glycosylation on IgG activity. Advances in Experimental Medicine and Biology, 780, 113-124.
28. Nakagawa, H.; et al. (2007). Detection of altered N-glycan profiles in whole serum from rheumatoid arthritis patients. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 853, 133-137.
29. Gornik, I.; et al. (1999). Fucosylation of IgG heavy chains is increased in rheumatoid arthritis. Clinical Biochemistry, 32, 605-608.
30. Guo, N.; et al. (2005). Repeated immunization induces the increase in fucose content on antigen-specific IgG N-linked oligosaccharides. Clinical Biochemistry, 38, 149-153.
31. Rademacher, T. W.; et al. (1986). Immunoglobulin G as a glycoprotein. Biochemical Society Symposia, 51, 131-148.
32. Galili, U. (1999). Evolution of alpha 1, 3 galactosyltransferase and of the alpha-Gal epitope. SubCellular Biochemistry, 32, 1-23.
33. Vanhove, B.; et al. (1998). Intracellular expression in pig cells of anti-alpha 1, 3 galactosyltransferase single-chain FV antibodies reduces Gal alpha 1, 3 Gal expression and inhibits cytotoxicity mediated by anti-Gal xenoantibodies. Transplantation, 66, 1477-1485.
34. Cox, K. M.; et al. (2006). Glycan optimization of a human monoclonal antibody in the aquatic plant Lemna minor. Nature Biotechnology, 24, 1591-1597.
35. Hamilton, S. R.; et al. (2003). Production of complex human glycoproteins in yeast. Science, 301, 1244-1246.
36. Strasser, R.; et al. (2008). Generation of glyco-engineered Nicotiana benthamiana for the production of monoclonal antibodies with a homogeneous human-like N-glycan structure. Plant Biotechnology Journal, 6, 392-402.
37. Schuster, M.; et al. (2007). In vivo glyco-engineered antibody with improved lytic potential produced by an innovative non-mammalian expression system. Biotechnology Journal, 2, 700-708.
38. Li, H.; et al. (2006). Optimization of humanized IgGs in glycoengineered Pichia pastoris. Nature Biotechnology, 24, 210-215.
39. Mett, V.; et al. (2008). Plants as biofactories. Biologicals, 36, 354-358.
40. Warner, T. G. (1999). Enhancing therapeutic glycoprotein production in Chinese hamster ovary cells by metabolic engineering endogenous gene control with antisense DNA and gene targeting. Glycobiology, 9, 841-850.
41. Adair, J. R. (1992). Engineering antibodies for therapy. Immunological Reviews, 130, 5-40.
42. Friend, P. J.; et al. (1999). Phase I study of an engineered aglycosylated humanized CD3 antibody in renal transplant rejection. Transplantation, 68, 1632-1637.
43. Hale, G.; et al. (2010). Pharmacokinetics and antibody responses to the CD3 antibody otelixizumab used in the treatment of type 1 diabetes. Journal of Clinical Pharmacology, 50, 1238-1248.
44. Wiczling, P.; et al. (2010). Pharmacokinetics and pharmacodynamics of a chimeric/humanized anti-CD3 monoclonal antibody, otelixizumab (TRX4), in subjects with psoriasis and with type 1 diabetes mellitus. Journal of Clinical Pharmacology, 50, 494-506.
45. Keymeulen, B.; et al. (2010). Four-year metabolic outcome of a randomised controlled CD3-antibody trial in recent-onset type 1 diabetic patients depends on their age and baseline residual beta cell mass. Diabetologia, 53, 614-623.
46. Schaer, D. A.; Cohen, A. D.; Wolchok, J. D. (2010). Anti-GITR antibodies - potential clinical applications for tumor immunotherapy. Current Opinion in Investigational Drugs, 11, 1378-1386.
47. Ng, C. M.; et al. (2006). Pharmacokinetics/pharmacodynamics of nondepleting anti-CD4 monoclonal antibody (TRX1) in healthy human volunteers. Pharmaceutical Research, 23, 95-103.
48. Mease, P.; et al. (2012). A phase II, double-blind, randomised, placebo-controlled study of BMS945429 (ALD518) in patients with rheumatoid arthritis with an inadequate response to methotrexate. Annals of the Rheumatic Diseases, 71, 1183-1189.
49. Eder, J. P.; et al. (2009). Novel therapeutic inhibitors of the c-Met signaling pathway in cancer. Clinical Cancer Research, 15, 2207-2214.
50. Morrison, S. L.; et al. (2002). Sequences in antibody molecules important for receptor-mediated transport into the chicken egg yolk. Molecular Immunology, 38, 619-625.
51. Wright, A.; Morrison, S. L. (1997). Effect of glycosylation on antibody function: implications for genetic engineering. Trends in Biotechnology, 15, 26-32.
52. Kuo, T. T.; Aveson, V. G. (2011). Neonatal Fc receptor and IgG-based therapeutics. MAbs, 3, 422-430.
53. Nimmerjahn, F.; Ravetch, J. V. (2011). FcgammaRs in health and disease. Current Topics in Microbiology and Immunology, 350, 105-125.
54. Huber, R.; et al. (1976). Crystallographic structure studies of an IgG molecule and an Fc fragment. Nature, 264, 415-420.
55. Deisenhofer, J. (1981). Crystallographic refinement and atomic models of a human Fc fragment and its complex with fragment B of protein A from Staphylococcus aureus at 2.9- and 2.8-A resolution. Biochemistry, 20, 2361-2370.
56. Dorai, H.; et al. (1991). Aglycosylated chimeric mouse/human IgG1 antibody retains some effector function. Hybridoma, 10, 211-217.
57. Krapp, S.; et al. (2003). Structural analysis of human IgG-Fc glycoforms reveals a correlation between glycosylation and structural integrity. Journal of Molecular Biology, 325, 979-989.
58. Feige, M. J.; et al. (2009). Structure of the murine unglycosylated IgG1 Fc fragment. Journal of Molecular Biology, 391, 599-608.
59. Houde, D.; et al. (2009). Characterization of IgG1 conformation and conformational dynamics by hydrogen/deuterium exchange mass spectrometry. Analytical Chemistry, 81, 2644-2651.
60. Davies, J.; et al. (2001). Expression of GnTIII in a recombinant anti-CD20 CHO production cell line: Expression of antibodies with altered glycoforms leads to an increase in ADCC through higher affinity for FC gamma RIII. Biotechnology and Bioengineering, 74, 288-294.
61. Shields, R. L.; et al. (2002). Lack of fucose on human IgG1N-linked oligosaccharide improves binding to human Fcgamma RIII and antibody-dependent cellular toxicity. Journal of Biological Chemistry, 277, 26733-26740.
62. Niwa, R.; et al. (2004). Enhancement of the antibody-dependent cellular cytotoxicity of low-fucose IgG1 Is independent of FcgammaRIIIa functional polymorphism. Clinical Cancer Research, 10, 6248-6255.
63. Niwa, R.; et al. (2004). Defucosylated chimeric anti-CC chemokine receptor 4 IgG1 with enhanced antibody-dependent cellular cytotoxicity shows potent therapeutic activity to T-cell leukemia and lymphoma. Cancer Research, 64, 2127-2133.
64. Niwa, R.; et al. (2005). IgG subclass-independent improvement of antibody-dependent cellular cytotoxicity by fucose removal from Asn297-linked oligosaccharides. Journal of Immunological Methods, 306, 151-160.
65. Niwa, R.; et al. (2005). Enhanced natural killer cell binding and activation by low-fucose IgG1 antibody results in potent antibody-dependent cellular cytotoxicity induction at lower antigen density. Clinical Cancer Research, 11, 2327-2336.
66. Suzuki, E.; et al. (2007). A nonfucosylated anti-HER2 antibody augments antibody-dependent cellular cytotoxicity in breast cancer patients. Clinical Cancer Research, 13, 1875-1882.
67. Ishida, T.; Ueda, R. (2007). Cancer therapy with antibodies. In M. Takatsu, K. Miyake, H. Yamamoto, & S. Taki (Eds.), Experiments manual for antibodies, revised second edition. Tokyo: Yodosya.
68. Koike, M. (2007). Development of therapeutic antibodies in allergic diseases. In M. Takatsu, K. Miyake, H. Yamamoto, & S. Taki (Eds.), Experiments manual for antibodies, revised second edition. Tokyo: Yodosya.
69. Scallon, B. J.; et al. (2007). Higher levels of sialylated Fc glycans in immunoglobulin G molecules can adversely impact functionality. Molecular Immunology, 44, 1524-1534.
70. Scallon, B.; et al. (2007). Quantitative in vivo comparisons of the Fc gamma receptor-dependent agonist activities of different fucosylation variants of an immunoglobulin G antibody. International Immunopharmacology, 7, 761-772.
71. Naso, M. F.; et al. (2010). Engineering host cell lines to reduce terminal sialylation of secreted antibodies. MAbs, 2, 519-527.
72. Anthony, R. M.; Ravetch, J. V. (2010). A novel role for the IgG Fc glycan: The anti-inflammatory activity of sialylated IgG Fcs. Journal of Clinical Immunology, 30(Suppl 1), S9-14.
73. Anthony, R. M.; et al. (2008). Recapitulation of IVIG anti-inflammatory activity with a recombinant IgG Fc. Science, 320, 373-376.
74. Jefferis, R. (1993). The glycosylation of antibody molecules: Functional significance. Glycoconjugate Journal, 10, 358-361.
75. Jefferis, R. (2009). Recombinant antibody therapeutics: The impact of glycosylation on mechanisms of action. Trends in Pharmacological Sciences, 30, 356-362.
76. Lund, J.; et al. (1996). Multiple interactions of IgG with its core oligosaccharide can modulate recognition by complement and human Fc gamma receptor I and influence the synthesis of its oligosaccharide chains. The Journal of Immunology, 157, 4963-4969.
77. Wright, A.; Morrison, S. L. (1994). Effect of altered CH2-associated carbohydrate structure on the functional properties and in vivo fate of chimeric mouse-human immunoglobulin G1. Journal of Experimental Medicine, 180, 1087-1096.
78. Lazar G. A.; et al. (2009). Optimized Fc variants and methods for their generation. US Patent 20090068175.
79. Sazinsky, S. L.; et al. (2008). Aglycosylated immunoglobulin G1 variants productively engage activating Fc receptors. Proceedings of the National Academy of Sciences of the United States of America, 105, 20167-20172.
80. Boruchov, A. M.; et al. (2005). Activating and inhibitory IgG Fc receptors on human DCs mediate opposing functions. Journal of Clinical Investigation, 115, 2914-2923.
81. Jung, S. T.; et al. (2011). Bypassing glycosylation: Engineering aglycosylated full-length IgG antibodies for human therapy. Current Opinion in Biotechnology, 22, 858-867.
82. Jung, S. T.; et al. (2010). Aglycosylated IgG variants expressed in bacteria that selectively bind FcgammaRI potentiate tumor cell killing by monocyte-dendritic cells. Proceedings of the National Academy of Sciences of the United States of America, 107, 604-609.
83. Chumsae, C.; et al. (2007). Comparison of methionine oxidation in thermal stability and chemically stressed samples of a fully human monoclonal antibody. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 850, 285-294.
84. Bhatt, N. P.; Patel, K.; Borchardt, R. T. (1990). Chemical pathways of peptide degradation. I. Deamidation of adrenocorticotropic hormone. Pharmaceutical Research, 7, 593-599.
85. Chi, E. Y.; et al. (2003). Roles of conformational stability and colloidal stability in the aggregation of recombinant human granulocyte colony-stimulating factor. Protein Science, 12, 903-913.
86. Wang, W. (2005). Protein aggregation and its inhibition in biopharmaceutics. International Journal of Pharmaceutics, 289, 1-30.
87. Gamble, C. N. (1966). The role of soluble aggregates in the primary immune response of mice to human gamma globulin. International Archives of Allergy and Applied Immunology, 30, 446-455.
88. Goldberg, D. S.; et al. (2010). Formulation development of therapeutic monoclonal antibodies using high-throughput fluorescence and static light scattering techniques: Role of conformational and colloidal stability. Journal of Pharmaceutical Science.
89. Raju, T. S.; Scallon, B. J. (2006). Glycosylation in the Fc domain of IgG increases resistance to proteolytic cleavage by papain. Biochemical and Biophysical Research Communications, 341, 797-803.
90. Zhu, J.; Yu, D. T. (2006). Matrix metalloproteinase expression in the spondyloarthropathies. Current Opinion in Rheumatology, 18, 364-368.
91. Kageyama, Y.; et al. (2000). Levels of rheumatoid factor isotypes, metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 in synovial fluid from various arthritides. Clinical Rheumatology, 19, 14-20.
92. Tao, M. H.; Morrison, S. L. (1989). Studies of aglycosylated chimeric mouse-human IgG. Role of carbohydrate in the structure and effector functions mediated by the human IgG constant region. The Journal of Immunology, 143, 2595-2601.
93. Raju, T. S.; et al. (2001). Glycoengineering of therapeutic glycoproteins: In vitro galactosylation and sialylation of glycoproteins with terminal N-acetylglucosamine and galactose residues. Biochemistry, 40, 8868-8876.
94. Raju, T. S.; Scallon, B. (2007). Fc glycans terminated with N-acetylglucosamine residues increase antibody resistance to papain. Biotechnology Progress, 23, 964-971.
95. Mimura, Y.; et al. (2000). The influence of glycosylation on the thermal stability and effector function expression of human IgG1-Fc: Properties of a series of truncated glycoforms. Molecular Immunology, 37, 697-706.
96. Hristodorov, D.; et al. (2012). Generation and comparative characterization of glycosylated and aglycosylated human IgG1 antibodies. Molecular Biotechnology. doi: 10.1007/s12033-012-9531-x
97. Gillespie, R.; et al. (2012). Cation exchange surface-mediated denaturation of an aglycosylated immunoglobulin (IgG1). Journal of Chromatography A, 1251, 101-110.
98. Ejima, D.; et al. (2007). Effects of acid exposure on the conformation, stability, and aggregation of monoclonal antibodies. Proteins, 66, 954-962.
99. Ishikawa, T.; et al. (2010). Influence of pH on heat-induced aggregation and degradation of therapeutic monoclonal antibodies. Biological & Pharmaceutical Bulletin, 33, 1413-1417.
100. Huang, L.; et al. (2005). In vivo deamidation characterization of monoclonal antibody by LC/MS/MS. Analytical Chemistry, 77, 1432-1439.
101. Bertolotti-Ciarlet, A.; et al. (2009). Impact of methionine oxidation on the binding of human IgG1 to Fc Rn and Fc gamma receptors. Molecular Immunology, 46, 1878-1882.
102. Pan, H.; et al. (2009). Methionine oxidation in human IgG2 Fc decreases binding affinities to protein A and FcRn. Protein Science, 18, 424-433.
103. Stockert, R. J. (1995). The asialoglycoprotein receptor: Relationships between structure, function, and expression. Physiological Reviews, 75, 591-609.
104. Lee, S. J.; et al. (2002). Mannose receptor-mediated regulation of serum glycoprotein homeostasis. Science, 295, 1898-1901.
105. Kanda, Y.; et al. (2007). Comparison of biological activity among nonfucosylated therapeutic IgG1 antibodies with three different N-linked Fc oligosaccharides: The high-mannose, hybrid, and complex types. Glycobiology, 17, 104-118.
106. Keck, R.; et al. (2008). Characterization of a complex glycoprotein whose variable metabolic clearance in humans is dependent on terminal N-acetylglucosamine content. Biologicals, 36, 49-60.
107. Jones, A. J.; et al. (2007). Selective clearance of glycoforms of a complex glycoprotein pharmaceutical caused by terminal N-acetylglucosamine is similar in humans and cynomolgus monkeys. Glycobiology, 17, 529-540.
108. Wawrzynczak, E. J.; et al. (1992). Blood clearance in the rat of a recombinant mouse monoclonal antibody lacking the N-linked oligosaccharide side chains of the CH2 domains. Molecular Immunology, 29, 213-220.
109. Swartz, J. R. (2001). Advances in Escherichia coli production of therapeutic proteins. Current Opinion in Biotechnology, 12, 195-201.
110. Andersen, D. C.; Reilly, D. E. (2004). Production technologies for monoclonal antibodies and their fragments. Current Opinion in Biotechnology, 15, 456-462.
111. Beck, A.; et al. (2008). Trends in glycosylation, glycoanalysis and glycoengineering of therapeutic antibodies and Fc-fusion proteins. Current Pharmaceutical Biotechnology, 9, 482-501.
112. Reichert, J. M. (2012). Marketed therapeutic antibodies compendium. MAbs, 4, 413-415.
113. Kamionka, M. (2011). Engineering of therapeutic proteins production in Escherichia coli. Current Pharmaceutical Biotechnology, 12, 268-274.
114. Caparon, M. H.; et al. (2010). Integrated solution to purification challenges in the manufacture of a soluble recombinant protein in E. coli. Biotechnology and Bioengineering, 105, 239-249.
115. Harrison, J. S.; Keshavarz-Moore, E. (1996). Production of antibody fragments in Escherichia coli. Annals of the New York Academy of Sciences, 782, 143-158.
116. Venturi, M.; Seifert, C.; Hunte, C. (2002). High level production of functional antibody Fab fragments in an oxidizing bacterial cytoplasm. Journal of Molecular Biology, 315, 1-8.
117. Huang, C. J.; Lowe, A. J.; Batt, C. A. (2010). Recombinant immunotherapeutics: Current state and perspectives regarding the feasibility and market. Applied Microbiology and Biotechnology, 87, 401-410.
118. Weir, A. N.; et al. (2002). Formatting antibody fragments to mediate specific therapeutic functions. Biochemical Society Transactions, 30, 512-516.
119. Humphreys, D. P.; et al. (2002). A plasmid system for optimization of Fab' production in Escherichia coli: Importance of balance of heavy chain and light chain synthesis. Protein Expression and Purification, 26, 309-320.
120. Chen, C.; et al. (2004). High-level accumulation of a recombinant antibody fragment in the periplasm of Escherichia coli requires a triple-mutant (degP prc spr) host strain. Biotechnology and Bioengineering, 85, 463-474.
121. Ramm, K.; Pluckthun, A. (2000). The periplasmic Escherichia coli peptidylprolyl cis, trans-isomerase FkpA. II. Isomerase-independent chaperone activity in vitro. Journal of Biological Chemistry, 275, 17106-17113.
122. Humphreys, D. P.; et al. (1996). Co-expression of human protein disulphide isomerase (PDI) can increase the yield of an antibody Fab' fragment expressed in Escherichia coli. FEBS Letters, 380, 194-197.
123. Lantry, L. E. (2007). Ranibizumab, a mAb against VEGF-A for the potential treatment of age-related macular degeneration and other ocular complications. Current Opinion in Molecular Therapeutics, 9, 592-602.
124. Goel, N.; Stephens, S. (2010). Certolizumab pegol. MAbs, 2, 137-147.
125. Simmons, L. C.; et al. (2002). Expression of full-length immunoglobulins in Escherichia coli: Rapid and efficient production of aglycosylated antibodies. Journal of Immunological Methods, 263, 133-147.
126. Reilly, D. E.; Yansura, D. G. (2010). Production of monoclonal antibodies in E. coli. In S. J. Shire, et al. (Eds.), Current trends in monoclonal antibodies development and manufacturing. New York: Springer.
127. Gasser, B.; Mattanovich, D. (2007). Antibody production with yeasts and filamentous fungi: On the road to large scale? Biotechnology Letters, 29, 201-212.
128. Zhang, N.; et al. (2011). Glycoengineered Pichia produced anti-HER2 is comparable to trastuzumab in preclinical study. MAbs, 3, 289-298.
129. Ohashi, H.; et al. (2010). A highly controllable reconstituted cell-free system - a breakthrough in protein synthesis research. Current Pharmaceutical Biotechnology, 11, 267-271.
130. Yin, G.; et al. (2012). Aglycosylated antibodies and antibody fragments produced in a scalable in vitro transcription-translation system. MAbs, 4.
131. Mureev, S.; et al. (2009). Species-independent translational leaders facilitate cell-free expression. Nature Biotechnology, 27, 747-752.
132. Knapp, K. G.; Goerke, A. R.; Swartz, J. R. (2007). Cell-free synthesis of proteins that require disulfide bonds using glucose as an energy source. Biotechnology and Bioengineering, 97, 901-908.
133. Jewett, M. C.; Swartz, J. R. (2004). Mimicking the Escherichia coli cytoplasmic environment activates long-lived and efficient cell-free protein synthesis. Biotechnology and Bioengineering, 86, 19-26.
134. Liu, D. V.; Zawada, J. F.; Swartz, J. R. (2005). Streamlining Escherichia coli S30 extract preparation for economical cell-free protein synthesis. Biotechnology Progress, 21, 460-465.
135. Zawada, J. F.; et al. (2011). Microscale to manufacturing scale-up of cell-free cytokine production - a new approach for shortening protein production development timelines. Biotechnology and Bioengineering, 108, 1570-1578.
136. De Jaeger, G.; et al. (2002). Boosting heterologous protein production in transgenic dicotyledonous seeds using Phaseolus vulgaris regulatory sequences. Nature Biotechnology, 20, 1265-1268.
137. Marillonnet, S.; et al. (2004). In planta engineering of viral RNA replicons: Efficient assembly by recombination of DNA modules delivered by Agrobacterium. Proceedings of the National Academy of Sciences of the United States of America, 101, 6852-6857.
138. Marillonnet, S.; et al. (2005). Systemic Agrobacterium tumefaciens-mediated transfection of viral replicons for efficient transient expression in plants. Nature Biotechnology, 23, 718-723.
139. Gomord, V.; et al. (2005). Biopharmaceutical production in plants: Problems, solutions and opportunities. Trends in Biotechnology, 23, 559-565.
140. Bardor, M.; et al. (2003). Monoclonal C5-1 antibody produced in transgenic alfalfa plants exhibits a N-glycosylation that is homogenous and suitable for glyco-engineering into human-compatible structures. Plant Biotechnology Journal, 1, 451-462.
141. Schahs, M.; et al. (2007). Production of a monoclonal antibody in plants with a humanized N-glycosylation pattern. Plant Biotechnology Journal, 5, 657-663.
142. Bardor, M.; et al. (2003). Immunoreactivity in mammals of two typical plant glyco-epitopes, core alpha(1,3)-fucose and core xylose. Glycobiology, 13, 427-434.
143. Kurosaka, A.; et al. (1991). The structure of a neural specific carbohydrate epitope of horseradish peroxidase recognized by anti-horseradish peroxidase antiserum. Journal of Biological Chemistry, 266, 4168-4172.
144. Faye, L.; et al. (1993). Affinity purification of antibodies specific for Asn-linked glycans containing alpha 1 → 3 fucose or beta 1 → 2 xylose. Analytical Biochemistry, 209, 104-108.
145. Bencurova, M.; et al. (2004). Specificity of IgG and IgE antibodies against plant and insect glycoprotein glycans determined with artificial glycoforms of human transferrin. Glycobiology, 14, 457-466.
146. Jin, C.; et al. (2006). Immunoglobulin G specifically binding plant N-glycans with high affinity could be generated in rabbits but not in mice. Glycobiology, 16, 349-357.
147. Schouten, A.; et al. (1996). The C-terminal KDEL sequence increases the expression level of a single-chain antibody designed to be targeted to both the cytosol and the secretory pathway in transgenic tobacco. Plant Molecular Biology, 30, 781-793.
148. Ko, K.; et al. (2003). Function and glycosylation of plant-derived antiviral monoclonal antibody. Proceedings of the National Academy of Sciences of the United States of America, 100, 8013-8018.
149. Bakker, H.; et al. (2006). An antibody produced in tobacco expressing a hybrid beta-1,4-galactosyltransferase is essentially devoid of plant carbohydrate epitopes. Proceedings of the National Academy of Sciences of the United States of America, 103, 7577-7582.
150. Bakker, H.; et al. (2001). Galactose-extended glycans of antibodies produced by transgenic plants. Proceedings of the National Academy of Sciences of the United States of America, 98, 2899-2904.